ORIGINAL ARTICLE J Bone Miner Metab (2005) 23:76–83 © Springer-Verlag Tokyo 2005 DOI 10.1007/s00774-004-0544-9 Nuray Öksüz Kanbur · Orhan Derman · Erol Kınık The relationships between pubertal development, IGF-1 axis, and bone formation in healthy adolescents Received: November 17, 2003 / Accepted: May 19, 2004 N.Ö. Kanbur (*) · O. Derman · E. Kınık Section of Adolescent Medicine, Department of Pediatrics, Hacettepe University Faculty of Medicine, 06100 Ankara, Turkey Tel. 90-312-305 1160; Fax 90-312-324 3284 e-mail: nuraykanbur@hotmail.com Abstract As IGF-1 is the major factor that affects bone growth, and both osteocalcin and bone-specific alkaline phosphatase are important markers of bone formation dur- ing puberty, there must be a relationship between these markers that does not change according to sex. The aim of this study was to investigate the relationships between pu- bertal development, the IGF-1 axis, and bone formation in healthy adolescents. Two hundred and five healthy children and adolescents were included in this cross-sectional study. Tanner’s classification was used to determine the pubertal developmental stage. Serum IGF-1 levels and IGF-1/ IGFBP-3 ratios increased with advancing pubertal stages, and maximum mean values were found at stages III–IV in girls and at stage IV in boys. Serum IGF-1 and IGFBP-3 levels were significantly correlated with osteocalcin and bone-specific alkaline phosphatase levels in boys, but not in girls. This difference between the sexes, and the relation of the IGF-1 axis to increased bone formation during puberty in both sexes, can be explained by the rate of increase of the IGF-1/IGFBP-3 ratio. We conclude that the timing of the increased bone formation rate during puberty; that is, the timing of the pubertal growth spurt, is determined by the maximum increase rate of the IGF-1/IGFBP-3 ratio. But this new hypothesis needs to be supported by longitudi- nal studies. Key words Puberty · Osteocalcin · Bone-specific alkaline phosphatase · IGF-1 · IGFBP-3 Introduction During the pubertal growth spurt, the rate of increase in height reaches its peak, and this is called “peak height velocity”. In the studies that were done by Tanner and colleagues, peak height velocity was observed at age 12 in girls and at age 14 in boys. Again, according to Tanner and colleagues, the pubertal growth spurt occurs at breast stage II–III in girls and at pubic hair stage III–IV in boys (Tanner et al. [1], Marshall and Tanner [2,3]). In puberty, in association with the growth spurt, the rate of bone growth also increases. Biochemical markers of bone formation and resorption increase along with longitudinal bone growth and bone remodeling. This increase is related to pubertal stage rather than to chronological age. It was shown that biochemical markers of bone turnover were maximal in Tanner stages II–III in girls and in Tanner stages III–IV in boys [4–6]. It is reported that osteocalcin and bone-specific alkaline phosphatase (BSALP) are the most sensitive markers of bone formation as indicators of skeletal development during puberty [4]. Insulin-like growth factor-1 (IGF-1) in the circulation is the major effector of bone growth and shows its mitogenic activities by mediating most of the physiological actions of growth hormone [7–11]. IGF-1 stimulates endochondral bone formation and rapidly activates bone turnover [12,13]. It is reported that IGF binding protein-3 (IGFBP-3), which is the major binding protein of IGF-1, has a direct role in the endocrine regulation of bone metabolism [14]. Both total IGF-1 and IGFBP-3 serum levels increase in puberty [15]. Furthermore, the molar ratio between IGF-1 and IGFBP-3 increases in puberty, suggesting that free IGF-1 increases in puberty when growth velocity is high. This is also shown by measuring serum free IGF-1 levels [16,17]. In the literature, there are many studies investigating serum osteocalcin or IGF-1 levels separately in relation to age and sexual developmental stages, but there are few studies investigating both bone-formation markers and the IGF-1 axis and the interrelationships between these param- eters during pubertal development. As the results of these few studies conflict with each other, this is still an area for investigation. The aim of this study was to investigate the relationships between pubertal development, the IGF-1 axis, and bone formation in healthy adolescents.